Safety and efficacy of liposomal irinotecan as the second-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis.

INTRODUCTION: The use of nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and increased area under the concentration-time curve. However, comprehensive systematic reviews or meta-analyses evaluating its efficacy as a second-line treatment have been scarce. Therefore, this study aims to review the current body of evidence on nal-IRI, assessing its overall clinical performances regarding the disease. METHODS: A systemic literature search was conducted based on articles published before September 26, 2023 in PubMed, Cochrane Library, EMBASE, and Web of Science databases. The fixed effect model was performed to calculate pooled mean difference and odds ratio for essential outcomes, such as overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. RESULTS: A total of 21 studies, including 3017 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, together with 5-fluorouracil and leucovorin, resulted in significantly improved PFS and OS, with a pooled mean difference of 1.01 months (95% confidence interval (95%CI)=0.97-1.05, p<0.01) and 0.29 months (95% CI=0.18-0.39, p<0.01) respectively; a pooled risk ratio of 2.06 (95%CI=1.30-3.27, p=0.002) for ORR compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted. CONCLUSION: Nal-IRI-based second-line treatments exhibited significantly improved PFS, OS and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). METHODS: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). RESULTS: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 - 89.0] vs.5.8 [IQR, 2.0 - 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 - 83.3] vs. 5.2 [IQR, 1.7 - 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). CONCLUSION: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.

Favorable Mortality-to-Incidence Ratio Trends of Lung Cancer in Countries with High Computed Tomography Density.

Background and Objectives: The prognoses of lung cancer deteriorate dramatically as the cancer progresses through its stages. Therefore, early screening using techniques such as low-dose computed tomography (LDCT) is critical. However, the epidemiology of the association between the popularization of CT and the prognosis for lung cancer is not known. Materials and Methods: Data were obtained from GLOBOCAN and the health data and statistics of the World Health Organization. Mortality-to-incidence ratios (MIRs) and the changes in MIR over time (δMIR; calculated as the difference between MIRs in 2018 and 2012) were used to evaluate the correlation with CT density disparities via Spearman's rank correlation coefficient. Results: Countries with zero CT density presented a relatively low incidence crude rate and a relatively high MIR in 2018 and a negative δMIR. Conversely, countries with a CT density over 30 had a positive δMIR. The CT density was significantly associated with the HDI score and MIR in 2018, whereas it demonstrated no association with MIR in 2012. The CT density and δMIR also showed a significant linear correlation. Conclusions: CT density was significantly associated with lung cancer MIR in 2018 and with δMIR, indicating favorable clinical outcomes in countries in which CT has become popularized.

Improved Trends in the Mortality-to-Incidence Ratios for Liver Cancer in Countries with High Development Index and Health Expenditures.

Primary liver cancer is one of the leading causes of death globally. Liver cancer has a unique geographical distribution, as its etiologies include chronic viral infections and aging. We hypothesize that the human development index (HDI), current health expenditure (CHE) per capita, and CHE-to-gross domestic product ratio (CHE/GDP) influence the incidence, mortality, and mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data were obtained from the Global Cancer Observatory (GLOBOCAN) database and the World Health Organization. MIRs and the changes in MIR over time (δMIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The crude incidence and mortality were significantly associated with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between δMIR and HDI, as well as between δMIR and CHE per capita. However, there were no significant associations between δMIR and CHE/GDP. Evidently, a favorable liver cancer δMIR was not associated with CHE/GDP, although it had a significant association with HDI and CHE per capita. These results are worthy of the attention of public health systems in correlation to improved outcomes in liver cancer.

Engineered Immature Testicular Tissue by Electrospun Mats for Prepubertal Fertility Preservation in a Bioluminescence Imaging Transgenic Mouse Model.

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.

Efficacy of cationic amphiphilic antihistamines on outcomes of patients treated with immune checkpoint inhibitors.

BACKGROUND: Cationic amphiphilic antihistamines have been shown to improve patient outcomes in immunogenic tumours, but whether they can augment and improve response to immunotherapy is unknown. We aim to evaluate the effect of cationic amphiphilic antihistamines in patients receiving immune checkpoint inhibitors (ICIs). METHODS: We conducted a retrospective propensity score-matched cohort study at two tertiary referral centres in Taiwan between January 2015 and December 2021. Patients who received desloratadine, cyproheptadine, and ebastine were classified as cationic amphiphilic antihistamine users. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and clinical benefit rate. Patients treated with cationic amphiphilic antihistamines were matched to patients who received non-cationic amphiphilic antihistamines based on variables including age, cancer type, stage, and history of allergic diseases. RESULTS: A total of 734 ICI-treated patients were included. After matching, 68 cationic amphiphilic antihistamine and non-cationic amphiphilic antihistamine users remained for analysis. Compared with non-cationic amphiphilic antihistamine users, patients who received cationic amphiphilic antihistamines had a significantly longer median overall survival (24.8 versus 10.4 months; Log-rank, p = 0.018) and progression-free survival (10.6 versus 4.93 months; Log-rank, p = 0.004). The use of cationic amphiphilic antihistamines was associated with an approximately 50% lower risk of all-cause mortality (HR, 0.55 [95% CI: 0.34-0.91]). Survival benefits were not seen in patients who received cationic amphiphilic antihistamines before immune checkpoint blockade. These survival benefits were observed regardless of the generation of cationic amphiphilic antihistamines. CONCLUSION: The use of cationic amphiphilic antihistamines was associated with improved survival among patients treated with immunotherapy.

Tracking Immature Testicular Tissue after Vitrification In Vitro and In Vivo for Pre-Pubertal Fertility Preservation: A Translational Transgenic Mouse Model.

Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation.

Risk of Ankylosing Spondylitis in Patients With Endometriosis: A Population-Based Retrospective Cohort Study.

Objectives: Previous research has shown a possible relationship between endometriosis and autoimmune diseases. However, the relationship between endometriosis and ankylosing spondylitis (AS) is lacking. Therefore, we intended to find possible associations between endometriosis and AS using ICD-9 coding data in a population-based retrospective cohort study in Taiwan. Method: Data for this retrospective cohort study were collected from the Taiwan National Health Insurance Research Database (NHIRD) between 2000-2012. We collected 13,145 patients with endometriosis and a 78,870 non-endometriosis comparison cohort. Diagnoses of endometriosis and AS were defined by the International Classification of Diseases-9 (ICD-9-CM) code for at least 3 outpatients or 1 hospitalization. Propensity score matching by comorbidities, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) usage were done for baseline comparability. Cox proportional hazard models were used to evaluate crude and adjusted hazard ratios. Results: The cumulative incidence of AS was higher in patients with endometriosis compared to the non-endometriosis comparison cohort (log-rank test, p = 0.015). The adjusted hazard ratio (aHR) of incidental AS in patients with endometriosis was 1.61 (95% CI = 1.11 to 2.35) in comparison to the non-endometriosis comparison cohort. An increased risk of AS was also observed in subjects with major depressive disorder (aHR = 5.05, 95% CI = 1.85 to 13.78). Stratified analyses of age subgroups showed consistent results. NSAID users had a lower risk of AS than NSAID non-users (aHR 4.57 vs 1.35, p for interaction = 0.031). Conclusions: In this retrospective population-based cohort study, we found a higher risk of AS in patients with endometriosis. We suggest that clinicians should pay attention to the occurrence of AS in patients with endometriosis.

NPS-1034 Induce Cell Death with Suppression of TNFR1/NF-κB Signaling in Testicular Cancer.

Background and objectives: NPS-1034 with a dual inhibitory effect on Met and Axl kinase receptors has exhibited therapeutic potential in previous models. However, no study on treating testicular cancer (TC) cell lines with NPS-1034 has been established. Materials and Methods: In this study, a series of in vitro examinations of the apoptotic effect induced by NPS-1034 in TC cell lines was conducted to clarify the molecular interactions involved. Results: A decrease in cell viability rate was observed following NPS-1034 treatment, as shown in the MTT assay. Induction of the apoptotic effect was observed in TC cells as the sub-G1 and Annexin-PI populations increased in a dose-dependent manner. The involvement of the tumor receptor necrosis factor receptor 1 (TNFR1) pathway was later determined by the proteome array and western blotting. A reduction in TNFR1 and NF-κB downstream protein expressions, an upregulation of cleaved caspase-3 and -7, and a downregulation of survivin and claspin all reassured the underlying mechanism of the TNFR1 involved in the apoptotic pathway induced by NPS-1034. Conclusions: Our findings provide evidence for a potential underlying TNFR1 pathway involved in NPS-1034 treatment. This study should offer new insights into targeted therapy for TC.